Uterine Tumors Resembling Ovarian Sex Cord Tumors

Abstract

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs), first characterized by Drs Clement and Scully in 1976, are rare neoplasms showing clinical, morphologic, and immunohistochemical overlap with a number of other uterine tumors, most being mesenchymal. Criteria for aggressive behavior are not clearly established. We report 75 tumors from patients ranging from 21 to 84 (mean=52.4) years. Seventy-one patients were treated by hysterectomy and 4 by conservative total excision. Thirty-eight tumors were intramyometrial, 34 submucosal, and 3 cervical; they ranged from 0.6 to 20 (mean=4.9) cm and were typically tan-yellow. Sixty-eight neoplasms were well-circumscribed and 7 had infiltrative borders (4 only minimally). In 56 tumors, a smooth muscle component was intimately admixed with the neoplastic cells (“pseudoinfiltration”; extensive in 29). Architectural patterns included cords (n=53), diffuse (n=51), hollow tubules (n=48), nests (n=38), trabeculae (n=37), retiform (n=23), solid tubules (n=21), pseudoangiomatoid (n=11), pseudopapillary (n=4), and whorled (n=2); typically, more than 1 pattern was seen. Tumor cells were epithelioid (n=62), epithelioid and spindled (n=12), or spindled (n=1) and/or rhabdoid (n=20; extensive in 2). Cytologic atypia was absent to mild in 57, moderate in 16, and moderate to severe in 2 tumors. Fifty-seven UTROSCTs had ≤2mitoses/10 high power fields (HPF), 12 had 3 to 5/10 HPF, and 6 >5/10 HPF. Necrosis was present in 3 and lymphovascular invasion in 1. Tumor cells showed a polyphenotypic immunohistochemical profile (with positivity for sex cord, smooth muscle, and epithelial markers), most commonly inhibin (17/33+) and calretinin (22/31+) positive. Five of 58 patients with follow-up (22 to 192; mean=73.2 mo) had recurrences/metastases from 30 to 144 months, and 2 died of disease. Malignant tumors showed >3 of the following 5 features compared with benign tumors: size >5 cm, at least moderate cytologic atypia, ≥3 mitoses/10 HPF, infiltrative borders, and necrosis. One of the 5 malignant tumors showed an extensive rhabdoid morphology. UTROSCTs are uncommon, show a wide morphologic spectrum, often pose problems in differential diagnosis, and typically have a benign outcome. Rare tumors are associated with late recurrences and a combination of more than 3 of the 5 features listed above predicted aggressive behavior in this series.

Uterine Tumor Resembling Ovarian Sex Cord Tumors: 23 Cases Indicating Molecular Heterogeneity With Variable Biological Behavior

“…38,39 There was no expression of HMB45 in 9 UTROSCT cases in the literature 36 and no expression of melanocytic markers (11 of Melanin-A and 2 of HMB45) in our series, though occasionally Melanin-A was expressed in the individual case. 11,36 Therefore, comprehensive morphological observation and polyphenotypic immunohistochemical profile are important for differential diagnosis of UTROSCTs. However, molecular detection is preferred for those cases with overlapping morphology features.…”

“…It was recently reported that ESR1::NCOA2/3 rearrangement was also found in adenosarcoma with sex cord differentiation 35 . However, a biphasic growth pattern with phyllodes-like architecture and periglandular stromal condensation of adenosarcomas is absent in UTROSCTs 36 . The distinction from epithelioid smooth muscle tumors is challenging in our series, mainly due to the small proportion of indistinct sex cord differentiation in GREB1 -rearranged tumors.…”

“…HMB45 was at least focal (usually strong) positive in TSC patients or patients with TFE alterations, with 79% of cases having expression in more than 50% of the tumor cells, while the tumors lacking TSC or TFE alterations were strongly positive in 10% of cells, and Melanin-A was expressed in 77% of PEComas 38,39 . There was no expression of HMB45 in 9 UTROSCT cases in the literature 36 and no expression of melanocytic markers (11 of Melanin-A and 2 of HMB45) in our series, though occasionally Melanin-A was expressed in the individual case 11,36 . Therefore, comprehensive morphological observation and polyphenotypic immunohistochemical profile are important for differential diagnosis of UTROSCTs.…”

“…35 However, a biphasic growth pattern with phyllodes-like architecture and periglandular stromal condensation of adenosarcomas is absent in UTROSCTs. 36 The distinction from epithelioid smooth muscle tumors is challenging in our series, mainly due to the small proportion of indistinct sex cord differentiation in GREB1-rearranged tumors. The coexpression pattern of myogenic markers and epithelial markers is observed in smooth muscle tumors, with usually diffuse and strong expression in smooth muscle tumors rather than the focal or patchy expression in UTROSCTs.…”

“…In the previous study of 34 patients with follow-up to date, only the presence of necrosis and significant mitotic activity (≥2/10 HPFs) were identified as associated with recurrence 6 . In the recent study of 75 UTROSCTs, they indicated the malignant tumors showed >3 of the following 5 features compared with benign tumors: size >5 cm, at least moderate cytologic atypia, ≥3 mitoses/10HPF, infiltrative borders, and necrosis 36 . However, in our cohort, only 2 of 7 recurrent cases had more than 2/10 HPFs mitoses in their primary tumors.…”